In developed countries, epithelial ovarian carcinoma (EOC) remains the most lethal gynecologic malignancy and the fourth or fifth most common cause of death from all cancers in women. To date, however, there are no means for early detection of ovarian cancer, nor is there a definitive system for accurately determining the classification of these tumors. The fatality of this disease stems from the frequent lack of symptoms until the tumors have disseminated beyond the ovary. As a result, the five-year survival rate of women with ovarian cancer remains a low and discouraging 40-50% [American Cancer Society, 2003; Jemal, A. et al., 2003]. If the tumor is still confined to the ovary, the chances of survival increase to a substantial 80-90%. Despite the clinical importance of EOC, the early progression of the disease is still poorly understood.
Over 85% of ovarian neoplasms, including carcinomas, cystadenomas and borderline tumors are thought to arise from the ovarian surface epithelium (OSE) or its derivatives, epithelial crypts and inclusion cysts [Scully, R E, 2000; Auersperg, N. et al., 2001]. The OSE is a simple mesothelium covering the ovary. As OSE progresses to malignancy, it acquires characteristics of the more complex Mullerian duct-derived epithelia of the oviduct, endometrium, or endocervix [Scully, R. E. et al., 1998]. Like these epithelia; differentiated ovarian carcinomas form glandular and papillary structures and acquire more highly specialized and complex epithelial characteristics, including E-cadherin [Maines-Bandiera, S. L. and Auersperg, N., 1997; Sundfeldt, K. et al., 1997; Davies, B. R. et al., 1998] and CA-125 [Bast, R. C. Jr. et al., 1998]. Thus, in contrast to other tissues where carcinogenesis is accompanied by a loss in differentiation, malignant OSE acquires a more highly differentiated epithelial phenotype, along the lines of Mullerian duct derivatives. These changes may reflect the common embryonic origin from which the OSE and Mullerian duct epithelia are derived, the urogenital coelomic epithelium [Scully, R. E., 2000].
Mullerian differentiation is so frequent in ovarian neoplasms that it serves as the basis for the classification of these tumors [American Cancer Society, 2003]. The most common type of ovarian cancer are the serous carcinomas which resemble oviductal epithelium. Except for CA125, there are at present no molecular markers that characterize tubal differentiation and serve as predictive or diagnostic markers in ovarian cancer [Bast, R. C. Jr. et al., 1998; Hellstrom, I. et al., 2003; Mazurek, A. et al., 1998].
OGP, oviduct-specific glycoprotein, is a specific tubal differentiation marker [Rapisarda, J. J. et al., 1993; Arias, E. B. et al., 1994; Lesse, H. J. et al., 2001]. OGP is normally secreted specifically and exclusively by the secretory epithelial cells of the oviduct, under estrogen dominance [Arias, E. B. et al., 1994; O'Day-Bowman, M. B. et al., 1995; Jaffe, R. C. et al., 1996]. It is more specific than CA125, which is normally also produced by the endometrium and endocervix [Kabawat, S. E. et al., 1983]. The human genome contains a single copy of the OGP gene located on chromosome 1p13 [Lapensee, L. et al., 1997]. It is a heavily glycosylated protein, like CA125, with a molecular weight of 110- to 130-kDa and is believed to play a role in fertilization and early embryonic development [Verhage, H. G. et al., 1988; Boice, M. L. et al., 1990; Boatman, D. E. and Magnoni, G. E., 1995; O'Day-Bowman, M. B. et al., 1996; Schmidt, A. et al., 1997].